Page 46 - 《中国药房》2025年23期

复方蜥蜴散诱导细胞凋亡及自噬性死亡逆转胃癌顺铂耐药的机

制研究
Δ

1， 2 #
刘彩月 ，李 铮 ，李卫强 （1.宁夏医科大学中医学院，银川 750004；2.宁夏少数民族医药现代化教育部重
1＊
1
点实验室，银川 750004）
中图分类号 R285；R965 文献标志码 A 文章编号 1001-0408（2025）23-2924-06
DOI 10.6039/j.issn.1001-0408.2025.23.07

摘 要 目的 研究复方蜥蜴散通过核因子κB（NF-κB）/SNAIL信号通路逆转顺铂（DDP）耐药性胃癌细胞MKN45/DDP的耐药机
制。方法 将MKN45/DDP细胞分为模型组（20%正常大鼠血清）、DDP组（1.3 μg/mL DDP+20%胎牛血清）及复方蜥蜴散低、高剂
量含药血清+DDP 组（17.2、68.8 g/kg 复方蜥蜴散的 20% 含药血清+1.3 μg/mLDDP）。测定 MKN45/DDP 细胞的生存活力、凋亡水
平、自噬水平，检测细胞上清中微管相关蛋白1轻链3（LC3）含量，检测细胞中B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）表达
水平以及磷酸化NF-κB p65 （p-NF-κB p65）、SNAIL的蛋白表达水平；利用NF-κB通路激动剂肿瘤坏死因子α（TNF-α）进一步明确
复方蜥蜴散改善DDP耐药性的分子机制。结果 与模型组及DDP组比较，复方蜥蜴散低、高剂量含药血清+DDP组细胞存活率均
显著降低（P＜0.05），凋亡及自噬水平均显著升高（P＜0.05）；细胞中 Bcl-2（复方蜥蜴散低剂量含药血清+DDP 组除外）、p-NF-κB
p65、SNAIL蛋白表达水平均显著降低（P＜0.05），LC3含量和Bax蛋白表达水平均显著升高（P＜0.05）。复方蜥蜴散高剂量含药血
清+DDP可有效逆转TNF-α诱导的耐药细胞中LC3Ⅱ/LC3Ⅰ比值下降及Bax蛋白表达下调（P＜0.05）。结论 复方蜥蜴散含药血
清联合DDP可通过抑制NF-κB/SNAIL信号通路，诱导MKN45/DDP细胞凋亡及自噬性死亡，从而逆转该细胞的DDP耐药性。
关键词 复方蜥蜴散；MKN45/DDP细胞；顺铂；耐药性；自噬；凋亡；NF-κB/SNAIL信号通路

Study on the mechanism of Compound lizard powder on reversing cisplatin resistance in gastric cancer by
inducing apoptosis and autophagic death
LIU Caiyue ，LI Zheng ，LI Weiqiang （1. School of Traditional Chinese Medicine， Ningxia Medical University，
1
1
1， 2
Yinchuan 750004， China；2. Ningxia Key Laboratory of Modernization of Ethnic Minority Medicine， Ministry of
Education， Yinchuan 750004， China）
ABSTRACT OBJECTIVE To study the mechanism of Compound lizard powder on reversing cisplatin（DDP） resistance in
resistant gastric cancer cell MKN45/DDP through nuclear factor-κB （NF-κB）/SNAIL signaling pathway. METHODS MKN45/DDP
cells were divided into model group （20% normal rat serum）， DDP group （1.3 μg/mL DDP+20% fetal bovine serum） and
Compound lizard powder low- and high-dose drug-containing serum+DDP groups （17.2， 68.8 g/kg Compound lizard powder 20%
drug-containing serum+1.3 μg/mL DDP）. The viability， apoptosis and intracellular autophagosome of MKN45/DDP cells were
detected. The content of microtubule-associated protein 1 light chain 3 （LC3） in the cell supernatant was detected. The expressions
of B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， as well as the protein expression levels of phosphorylated NF-κB
p65 （p-NF-κB p65） and SNAIL were detected. The molecular mechanism of Compound lizard powder in improving DDP resistance
was further clarified by using NF-κB pathway agonist tumor necrosis factor-α （TNF-α）. RESULTS Compared with model group
and DDP group， the cell survival rates of Compound lizard powder low- and high-dose drug-containing serum+DDP groups were
significantly decreased （P＜0.05）， while the levels of apoptosis and autophagic death were significantly increased （P＜0.05）. The
expression levels of Bcl-2 （except for the compound lizard powder low-dose drug-containing serum+DDP group）， p-NF-κB p65
and SNAIL protein in MKN45/DDP cells were significantly decreased （P＜0.05）. The content of LC3 and expression of Bax
protein were significantly increased （P＜0.05）. High-dose Compound lizard powder drug-containing serum+DDP could effectively
reverse the down-regulation of LC3 Ⅱ/LC3 Ⅰ and Bax protein expression induced by TNF- α （P＜0.05）. CONCLUSIONS
Compound lizard powder drug-containing serum combined with DDP can induce apoptosis and autophagic death of MKN45/DDP
cells by inhibiting NF-κB/SNAIL signaling pathway， thus
Δ 基金项目 国家自然科学基金项目（No.82260916）；宁夏医科大
reversing DDP resistance of cells.
学科研项目（No.XZ2023012） KEYWORDS
＊第一作者 硕士研究生。研究方向：中医药防治肝病及脾胃病。 Compound lizard powder； MKN45/DDP
E-mail：1925622481@qq.com cells； cisplatin； resistance； autophagy； apoptosis； NF-κB/
# 通信作者 主任医师，教授，博士生导师。研究方向：中医药防治 SNAIL pathway
肝病及脾胃病。E-mail：lwq200309@163.com

· 2924 · China Pharmacy 2025 Vol. 36 No. 23 中国药房 2025年第36卷第23期